The objectives of this research program are to study the mechanisms by which Neisseria meningitidis attach to, colonize and invade human mucosal surfaces and to determine methods for blocking or altering those pathogenic mechanisms. A variety of techniques will be employed to study meningococcal ligands, human cell receptors, their interaction, and inhibition of their interaction by antibody. The techniques will include light and electron microscopy; quantitation of meningococcal attachment to human cells and mucosal surfaces as developed and previously used in this laboratory; purification of meningococcal surface components (e.g. pili, lipopolysaccharide and outer membrane proteins); enzymatic and chemical modification of meningococcal surface components (ligands) and human cell receptors; isolation of human cell receptors by analytical and preparative gel techniques; production of antibody to meningococcal surface components using mouse hybridoma cell lines, rabbits, or both; and use of organ cultures to study the interaction of meningococci with nasopharyngeal mucosa. The above studies should: 1) provide an understanding of the mechanisms that determine attachment of meningococci to human cells; 2) yield information concerning mechanisms by which meningococci invade the mucosal barrier to enter the bloodstream; and 3) aid in the development of an improved vaccine to prevent the devastating illnesses caused by meningococci.